This proposal is directed towards: 1) understanding the mechanism of action and physiological role of a subclass of the colony stimulating factors (CSF) that stimulates monuclear phagocyte proliferation (CSF-1) and 2) using purified CSF and its specific antibody as probes to investigate the early events in hemopoiesis. Working with murine and human material, attempts will be made as often as possible to apply murine findings to the human system. Studies on the mechanism of action will be carried out using biologically active 125I-CSF-1. The nature and distribution of CSF-1 binding cells in normal and leukemic murine and human cell populations will be examined. The mechanism of CSF-1 interaction with target cells, the relationship between target cell binding and responses and the characteristics of the CSF-1 'receptor' will be investigated. Parameters relating to blood cell differentiation and the mononuclear phagocytic system will be monitored in mice following injection of purified L cell CSF-1 and its specific antibody to determine the physiological role of CSF-1. Highly specific antibody to both L cell and human urinary CSF-1 will be prepared. These antibodies will be used to examine the nature and distribution of CSF-1 releasing cells and to examine the genetic control of human CSF-1 production using human-mouse cell hybrids. Studies of the mechanism by which pluripotent stem cells give rise to the most immature CSF-1-responsive cells will be commenced.